Drug-induced erythrocyte membrane internalization

In vitro erythrocyte membrane internalization, resulting in the formation of membrane-lined vacuoles, can be quantified by a radioisotopic method. A complex of (37)Co-labeled vitamin B(12) and its plasma protein binders is first adsorbed to the cell surface, and after vacuoles are formed, the nonint...

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Bibliographic Details
Published in:The Journal of clinical investigation 1972-07, Vol.51 (7), p.1833-1844
Main Authors: Ben-Bassat, I, Bensch, K G, Schrier, S L
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - blood
Calcium - blood
Chlorpromazine - pharmacology
Cytoplasm - drug effects
Erythrocyte Aging
Erythrocytes - cytology
Erythrocytes - drug effects
Ethylmaleimide - pharmacology
Fluorides - pharmacology
Humans
Hydrocortisone - pharmacology
Hydrogen-Ion Concentration
In Vitro Techniques
Magnesium - blood
Membranes - drug effects
Microscopy, Electron
Microscopy, Phase-Contrast
Primaquine - pharmacology
Sulfonic Acids - pharmacology
Vinblastine - pharmacology
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Summary:In vitro erythrocyte membrane internalization, resulting in the formation of membrane-lined vacuoles, can be quantified by a radioisotopic method. A complex of (37)Co-labeled vitamin B(12) and its plasma protein binders is first adsorbed to the cell surface, and after vacuoles are formed, the noninternalized label is removed by washing and trypsin treatment. The residual radioactivity represents trapped label and can be used to measure the extent of membrane internalization. Using this method, it was found that in addition to primaquine, a group of membrane-active drugs, specifically hydrocortisone, vinblastine, and chlorpromazine can induce membrane internalization in erythrocytes. This is a metabolic process dependent on drug concentration, temperature, and pH. Vacuole formation by all agents tested can be blocked by prior depletion of endogenous substrates or by poisoning the erythrocytes with sodium fluoride and sulfhydryl blocking agents. This phenomenon resembles in some respects the previously reported membrane internalization of energized erythrocyte ghosts. It is suggested that membrane internalization is dependent on an ATP-energized state and is influenced by the balance between the concentrations of magnesium and calcium in the membrane. This study provides a basis for proposing a unifying concept of the action of some membrane-active drugs, and for considering the role of erythrocyte membrane internalization in pathophysiologic events.
ISSN:0021-9738
DOI:10.1172/JCI106985